REVIEW ARTICLE

The new epidemiology of nosocomial bacterial infectionsin cirrhosis: therapeutical implications

Juan Acevedo • Anıbal Silva • Veronica Prado •

Javier Fernandez

Received: 11 May 2012 / Accepted: 25 July 2012 / Published online: 14 August 2012

� Asian Pacific Association for the Study of the Liver 2012

Abstract Cirrhotic patients are at increased risk of devel-

oping infection, sepsis and death. Enterobacteriaceae and

nonenterococcal streptococci are the main bacteria respon-

sible for spontaneous and urinary infections in this popula-

tion. Prompt and appropriate treatment is basic in the

management of cirrhotic patients with infection. Third-

generation cephalosporins continue to be the gold-standard

antibiotic treatment of the majority of infections acquired in

the community because responsible strains are usually sus-

ceptible to b-lactams. By contrary, nosocomial infections are

nowadays frequently caused by multiresistant bacteria

(extended-spectrum b-lactamase-producing Enterobacteri-

aceae, Pseudomonas aeruginosa, methicillin-resistant

Staphylococcus aureus, and vancomycin-resistant entero-

cocci among others) that are nonsusceptible to the main

antibiotics. Treatment of these infections requires the use of

broader spectrum antibiotics (carbapenems) or of antibiotics

that are active against specific resistant bacteria (glycopep-

tides, linezolid, daptomycin, amikacin and colistin).

Empirical antibiotic schedules must be adapted to the local

epidemiological pattern of antibiotic resistance. Careful

restriction of antibiotic prophylaxis to the high-risk popu-

lation is also mandatory to reduce the spread of multiresistant

bacteria in cirrhosis.

Keywords Liver cirrhosis � Nosocomial infection �Multiresistant bacteria

Abbreviations

SBP Spontaneous bacterial peritonitis

ICU Intensive care unit

HCA Healthcare-associated

GPC Gram-positive cocci

GNB Gram-negative bacilli

ESBL Extended-spectrum b-lactamase

MRSA Methicillin-resistant Staphylococcus aureus

VRE Vancomycin-resistant enterococci

Introduction

Patients with cirrhosis have an increased risk of developing

bacterial infection, sepsis, sepsis-induced organ failure and

death [1–3]. Infection is present at admission or develops

during hospitalization in about 25–35 % of patients [4, 5].

Mortality of infected patients with cirrhosis is higher than

that observed in the noncirrhotic population. It reaches

38 % at 1 month and can exceed 70 % in septic shock

[6–8]. Spontaneous bacterial peritonitis (SBP) is the most

frequent infection followed by urinary infection, pneumo-

nia, cellulitis and bacteremia. Clinical risk factors are high

Child–Pugh score, variceal bleeding, low ascitic protein

levels and prior episode of SBP [9–12]. Hospitalization,

especially if associated with invasive procedures and

J. Acevedo � A. Silva � V. Prado � J. Fernandez (&)

Liver Unit, Hospital Clinic, University of Barcelona,

Villarroel 170, 08036 Barcelona, Catalunya, Spain

e-mail: jfdez@clinic.ub.es

J. Acevedo � A. Silva � V. Prado � J. Fernandez

Institut d’Investigacions Biomediques August-Pi-Sunyer

(IDIBAPS), Barcelona, Spain

J. Acevedo � A. Silva � V. Prado � J. Fernandez

Centro de Investigacion Biomedica en Red de Enfermedades

Hepaticas y Digestivas (CIBEREHD), Barcelona, Spain

J. Acevedo

Hospital Sant Jaume de Calella, Calella, Spain

123

Hepatol Int (2013) 7:72–79

DOI 10.1007/s12072-012-9396-x

intensive care unit (ICU) admission, also increases the risk

of infection [4].

Recent data show that *30 % of bacterial infections

are community-acquired, 30 % are healthcare-associated

(HCA) (infections that occurred in the first 2 days of

admission in patients in contact with the healthcare envi-

ronment in the past 3 months; HCA), and 40 % are noso-

comial infections [5]. Epidemiology and clinical efficacy

of currently recommended empirical antibiotic treatment

(third-generation cephalosporins or amoxicillin-clavulanic

acid) differs markedly among them. b-lactams seem to be

ineffective in nosocomial and to a lesser extent in HCA

infections, feature that is related to the higher prevalence of

multiresistant (MR) bacteria in infections acquired in the

healthcare environment [5, 13–17]. The current review will

focus on these epidemiological differences and on their

therapeutic implications.

Initial epidemiological changes

Cirrhotic patients present several immune defects that

facilitate bacterial translocation induced by increased

intestinal permeability and gut bacterial overgrowth

[18–20]. Bacterial translocation plays a major role in the

pathogenesis of SBP and other spontaneous infections in

cirrhosis. Pathogens present in the skin and respiratory tract

can also translocate to the systemic circulation. As conse-

quence, Enterobacteriaceae and nonenterococcal strepto-

cocci cause the majority of spontaneous infections in the

cirrhotic population. The continuous pressure exerted by

antibiotics on this endogenous bacterial flora through long-

term norfloxacin prophylaxis and the extended use of third-

generation cephalosporins could have contributed to the

development of MR bacterial infections in cirrhosis.

In the last decades, clinical practice in Hepatology has

dramatically changed as consequence of the implementa-

tion of the liver transplant programs. Cirrhotic patients are

nowadays frequently admitted to the ICU and are submit-

ted to numerous diagnostic and therapeutic invasive pro-

cedures. This high degree of instrumentation of patients is

associated with a higher risk of secondary infections

caused by nonclassical pathogens. In 2002, we reported the

first prospective investigation assessing potential changes

in the epidemiology of bacterial infections in a large

number of patients with decompensated cirrhosis and

community-acquired or nosocomial infections [4]. This

study included 572 infections of which 39 % were noso-

comial. The first important finding of that study was an

increase in the rate of infections caused by Gram-positive

cocci (GPC) associated with the increasing use of invasive

procedures during hospitalization and treatments in the

ICU. The traditional preponderance of infections caused by

Gram-negative bacilli (GNB) characteristic of cirrhosis

was shifted to a higher prevalence of infection by GPC in

hospitalized patients. In community-acquired infections,

GNB continued to be the main cause of infection. The

second epidemiological change reported in the study was

the emergence of SBP by quinolone-resistant bacteria in

patients on long-term selective intestinal decontamination

with norfloxacin. This change, however, had no major

clinical effect on the empirical antibiotic treatment guide-

lines because quinolone-resistant bacteria were susceptible

to third-generation cephalosporins in most cases and the

prevalence of infections resulting from MR bacteria in this

series was \10 %.

New epidemiological changes: infections by MR

bacteria

Several studies have recently reported an increase in the

prevalence of infections caused by MR bacteria in cirrhosis

[5, 13–17, 21–23], an epidemiological change already

observed in the general population [24–26]. These bacteria

are pathogens that are resistant to the main antibiotics,

including b-lactams [27]. The most common are extended-

spectrum b-lactamase-producing Enterobacteriaceae

(ESBL), nonfermentable GNB as P. aeruginosa, Steno-

trophomonas maltophilia or Acinetobacter baumanii,

methicillin-resistant S. aureus (MRSA), vancomycin-sus-

ceptible Enterococcus (VSE), and vancomycin-resistant

Enterococcus (VRE). Epidemiological patterns of multire-

sistance are different among geographical areas and even

among hospitals. As an example, VRE and MRSA are more

prevalent in United States, meanwhile ESBL-producing

Enterobacteriaceae are predominant in South Europe and

Asia.

Data derived from studies performed in the general

population show that nosocomial pathogens are usually

much more resistant to antibiotics than those bacteria

acquired in the community [24–26]. However, this issue

has not been adequately addressed in cirrhosis. Only few

studies have reported a higher incidence of strains resistant

to b-lactams in nosocomial infections (33–78 %) compared

to community-acquired episodes (from 10 to 18 %) [13, 14,

18, 28, 29].

Prevalence and clinical characteristics of MR bacterial

infections in cirrhosis have been prospectively investigated

in a recent paper published by our group. This unicentric

study included 669 infections from two series of cirrhotic

patients collected in two different periods (2005–2007 and

2010–2011) [5]. A total of 32 % of infections were com-

munity-acquired, 30 % were HCA, and 38 % were noso-

comial. MR bacteria were more frequently isolated in

nosocomial infections (35 and 39 % in the first and second

Hepatol Int (2013) 7:72–79 73

123

series) compared to HCA (14 and 20 %, respectively) and

community-acquired episodes (4 and 0 %, respectively). In

the present study, ESBL-producing Enterobacteriaceae

was the most frequent MR strain isolated followed by

Enterococcus faecium, P. aeruginosa, and MRSA. The

type of MR bacteria varied among different infections.

ESBL-producing Enterobacteriaceae was the most fre-

quent MR bacteria isolated in SBP, urinary infections and

spontaneous bacteremia, MRSA predominated in cellulitis

and catheter infection and P. aeruginosa was most frequent

in nosocomial pneumonia.

Other groups have also reported an increasing prevalence

of SBP caused by ESBL-producing Enterobacteriaceae

(Table 1). b-lactamase hydrolyzes cephalosporins, aztreo-

nam, and extended-spectrum penicillin, rendering these anti-

biotics clinically ineffective. Rates of infection caused by this

MR bacteria vary among countries and range from 0 % in

Germany, to 5 % in France, 7–11 % in Korea, 12 % in

Turkey, and 20 % in Italy [4, 5, 12–15, 17, 21, 22, 30–35].

Another new problem that has been recently described

in the general population is the emergence of nosocomial

infections caused by bacteria that produce novel b-lacta-

mases with direct carbapenem-hydrolyzing activity. Several

reports have described the spread of carbapenemase-

producing Klebsiella pneumoniae across the world [36, 37].

This year an Italian group has published the first case of

nosocomial SBP due to carbapenemase-producing K. pneu-

moniae. Sporadic cases have also been observed in our liver

unit [38].

All these data confirm that epidemiological patterns of

antibiotic resistance differ markedly among different geo-

graphical areas and countries. Regular assessment of these

patterns of multiresistance is therefore recommended.

Clinical outcome of nosocomial and MR bacterial

infections in cirrhosis

Previous studies have reported conflicting results regarding

the prognosis of nosocomial infections in cirrhosis. Some

showed very high mortality rates (59–67 %) and other

figures are similar to those observed in community-

acquired episodes [13, 14, 18, 28, 29]. The worse prognosis

of nosocomial infections found by some authors could be

linked to the higher incidence of bacterial strains resistant

to b-lactams in hospital-acquired episodes. Recent data

from Spain clearly support this contention. In the study

mentioned previously [5], hospital mortality rate of noso-

comial infections (25 % in the first series and 48 % in the

second) was significantly higher than that observed in HCA

Table 1 Prevalence and risk factors of extended-spectrum b-lactamase-producing Enterobacteriaceae in spontaneous bacterial peritonitis

Author/year/ref Country Prevalence Risk factors

Fernandez et al. [4] Spain 1.5 % No data

Park et al. [21] Korea 7 % in 1995, 28 % in 1999 Previous exposition to quinolones or b-lactams

Current or recent hospitalization

Song et al. [13] Korea 14 % in community-acquired episodes No data

67 % in nosocomial infections

Cereto et al. [30] Spain 6 % in total series, 13 % in patients on quinolone prophylaxis Norfloxacin prophylaxis

Angeloni et al. [31] Italy 8 % HCA infections

Cheong et al., 2009 [14] Korea 6 % Previous exposition to b-lactams

Nosocomial infection

Song and Heo et al. [22, 32] Korea 7.5–11 % No data

Yakar et al. [33] Turkey 18 % No data

Piroth et al. [34] France 5 % No data

Umgelter et al. [35] Germany 0 % No data

Ariza et al. [15] Spain 1 % in community-acquired episodes Nosocomial infection

Previous exposition to b-lactams6 % in HCA infections

9 % in nosocomial episodes Diabetes mellitus

Upper gastrointestinal bleeding

Fernandez et al. [5]a Spain 0–2 % in community-acquired episodes Nosocomial infection

Long-term norfloxacin prophylaxis0–2 % in HCA infections

16–29 % in nosocomial episodes Previous exposition to b-lactams (3 months)

Recent infection by MR bacteria (6 months)

a Included two series of patients evaluated between 2005 and 2007 and between 2010 and 2011. The analysis of risk factors was performed for all infections

including SBP and nonSBP episodes

74 Hepatol Int (2013) 7:72–79

123

(9 and 23 %, respectively) and community-acquired epi-

sodes (7 and 21 %, respectively). The study also demon-

strated that infections caused by MR bacteria, which were

much more prevalent in infections acquired during hospi-

talization, had a very poor prognosis with higher incidence

of treatment failure (70 vs. 92 %; p \ 0.0001), septic

shock (26 vs. 10 %; p \ 0.0001), and hospital mortality

(25 vs. 12 %; p = 0.001) than those infections caused by

susceptible bacteria. The delay in the initiation of an

appropriate antibiotic treatment is without any doubt one of

the main explanations for this finding.

Risk factors for MR bacterial infections

The main risk factors described in the literature for the

development of infections caused by MR bacteria in the

general population are current or recent hospitalization,

healthcare support (outpatient clinic), and previous expo-

sure to antibiotics such as b-lactams or fluoroquinolones

[39–43]. Similar risk factors were identified in a recent

paper published by our group [5]. Nosocomial origin of

infection (HR 4.43), long-term norfloxacin prophylaxis

(HR 2.69), recent infection by MR bacteria (HR 2.45), and

recent use of b-lactams (HR 2.39) were independently

associated with the development of MR infections.

Prior infection by ESBL-producing Enterobacteriaceae,

nosocomial acquisition of the infection, and previous

treatment with b-lactams or norfloxacin are also indepen-

dent predictors of infection caused by this type of MR

bacteria. In contrary to what has been suggested by other

authors [17], HCA infections were not identified in the

present study as a risk factor for the development of MR

bacterial infections.

Empirical antibiotic treatment of bacterial infections

in cirrhosis

Empirical treatment should cover all potential organisms

responsible for infection without causing adverse effects.

Prompt and appropriate treatment is also essential in the

management of cirrhotic patients with infection. During

many years, third-generation cephalosporins have been

considered the gold-standard empirical antibiotic treatment

of many of the infections occurring in cirrhosis since they

are active against Enterobacteriaceae (antimicrobial mini-

mum inhibitory concentration: MIC value B1 mg/L) and

nonenterococcal streptococci (MIC B0.5 mg/L) and are

well tolerated [44–48]. Amoxicillin–clavulanic acid shows

similar efficacy, although MIC values for Enterobacteria-

ceae and some nonenterococcal streptococci are higher

(B8 mg/L). It is important to consider, however, that these

guidelines are based on studies performed in the 1980s and

1990s in a very different epidemiological scenario. At that

time, studies included mainly community-acquired infec-

tions, *70–80 % of the isolated organisms were GNB and

the great majority of them were susceptible to the main

antibiotics including quinolones (MIC B 0.5 mg/L) and

b-lactams (cephalosporins and penicillins). Mild and severe

infections by quinolone-resistant bacteria were reported

several years later as a direct consequence of the extended

use of norfloxacin in the prophylaxis of bacterial infections

in cirrhosis [4, 30, 49]. This finding, however, had no major

clinical effect on the empirical antibiotic treatment guide-

lines because quinolone-resistant bacteria continued to be

susceptible to third-generation cephalosporins in most cases.

The only change introduced in these recommendations was to

avoid quinolones in the empirical treatment of severe infec-

tions in patients on long-term norfloxacin prophylaxis. Cur-

rent guidelines still do not distinguish between community-

acquired and nosocomial infections [47, 48].

New epidemiological data show that third-generation

cephalosporins or amoxicillin–clavulanic acid is ineffec-

tive in a relevant proportion of nosocomial infections in

cirrhosis [5]. Currently, recommended empirical antibiotic

strategies show a very low efficacy in hospital-acquired

infections (40 %). This feature is observed across different

types of infections including SBP (26 %), urinary infec-

tions (29 %), and spontaneous bacteremia (18 %). Clinical

efficacy of empirical antibiotic treatment is also lower in

HCA infections (73 %) compared to community-acquired

episodes (83 %), particularly in pneumonia and urinary

tract infection. Other groups have also reported a decrease

in the clinical efficacy of the current guidelines for the

treatment of SBP with failure rates ranging between 26 and

41 % [31, 33, 35].

In our opinion, these data clearly indicate that empirical

antibiotic therapy of SBP and other bacterial infections in

cirrhosis should be selected according to not only the type and

severity of the infection but also its site of acquisition

(Figs. 1, 2).

Empirical antibiotic treatment of community-acquired

infections

Third-generation cephalosporins are still very effective in the

treatment of spontaneous infections acquired in the commu-

nity (SBP, spontaneous bacteremia, and spontaneous bacterial

empyema, SBE), with resolution rates of around 80 % [5].

Amoxicillin–clavulanic acid seems to show similar results [1].

Quinolones, an antibiotic broadly used in United States, are

not recommended in patients submitted to long-term nor-

floxacin prophylaxis or in geographical areas with a high

prevalence of quinolone-resistant bacteria [1, 47, 48].

Hepatol Int (2013) 7:72–79 75

123

Empirical treatment of community-acquired urinary

infections in cirrhosis includes b-lactams, quinolones, or

trimethoprim-sulfamethoxazole. b-lactams are also the

base of the treatment of community-acquired pneumonia

(in combination with levofloxacin, moxifloxacin, or a

macrolide) and cellulitis [1].

Empirical treatment of nosocomial infections

New guidelines for the treatment of nosocomial SBP and

other spontaneous infections in cirrhosis are clearly

needed. These empirical antibiotic strategies should con-

sider the local epidemiological patterns of multiresistance

(Table 2; Fig. 1) [1, 5]. In areas with a high prevalence of

ESBL-producing Enterobacteriaceae, carbapenems should

be used in the empirical treatment of nosocomial episodes

of SBP, SBE, and spontaneous bacteremia. This antibiotic

family is highly active against Enterobacteriaceae that

produce b-lactamases with MIC values B1 mg/L for do-

ripenem and B2 mg/L for meropenem and imipenem. A

glycopeptide (vancomycin or teicoplanin IV) should

also be added to this empirical treatment to cover

VSE (MIC B 4 and 2 mg/L, respectively) and MRSA

Fig. 1 Proposed algorithm for

the empirical treatment of

spontaneous infections

according to the site of

acquisition of the infection and

the presence of risk factors for

MR bacteria. *Infection by MR

bacteria in the last 6 months,

use of b-lactams in the last

3 months, and long-term use of

norfloxacin prophylaxis.

**Linezolid or daptomycin

should replace glycopeptides in

areas with a high prevalence of

VRE. SBP spontaneous

bacterial peritonitis;

SBE spontaneous bacterial

empyema; SB spontaneous

bacteremia

Fig. 2 Proposed algorithm for

the treatment of urinary

infections according to the

severity of the infection and its

site of acquisition. *Linezolid or

daptomycin should replace

glycopeptides in areas with a

high prevalence of VRE

76 Hepatol Int (2013) 7:72–79

123

(MIC B 2 mg/L) [1, 50]. In United States and other

regions with a high rate of infections caused by VRE,

glycopeptides must be replaced by linezolid or daptomycin.

Both antibiotics are active against GPC (MIC B 4 mg/L)

including those strains resistant to penicillin (VSE),

methicillin (MRSA), and vancomycin (VRE) [50].

Urinary infections acquired during hospitalization

should be treated with oral nitrofurantoin or fosfomycin (in

uncomplicated infections) or carbapenems plus glycopep-

tides in patients with sepsis to cover ESBL-producing

Enterobacteriacea and VSE. In areas with a high preva-

lence of VRE, linezolid or daptomycin should be used

instead of glycopeptides in patients with complicated uri-

nary infections (Table 2; Fig. 2) [1, 50].

Cellulitis should be treated with antibiotic active against

MRSA and P. aeruginosa (i.e., ceftazidime or meropenem

plus glycopeptide). Empirical treatment of nosocomial

pneumonia should follow the local guidelines suggested for

the noncirrhotic population (Table 2) [1].

Moreover, an appropriate control of infection is needed.

Patients with MR bacterial infections must be isolated during

hospitalization [25, 51]. In addition, antibiotic strategies that

include the restrictive use of b-lactams (in the treatment of

infections) and quinolones (in their prophylaxis) in cirrhosis

are mandatory to prevent the spread of MR bacteria. In line

with this policy of antibiotic restriction, de-escalation to the

most appropriate antibiotic should be done early after know-

ing the results of the microbiological tests [1].

Empirical treatment of HCA infections

Third-generation cephalosporins or amoxicillin–clavulanic

acid is still effective in the treatment of some HCA

infections such as SBP (resolution rate 71 % compared to

78 % in CA infections) or cellulitis (resolution rate 81 vs.

82 % in CA infections). Their efficacy is, however, lower

in HCA pneumonia (33 %) and urinary infections (59 %)

[5]. In our opinion, empirical antibiotic strategies for these

two infections and for patients with HCA SBP with several

risk factors of MR bacterial infections and/or severe sepsis

or shock should also follow those strategies described for

nosocomial infections (Figs. 1, 2; Table 2).

Antibiotic options in difficult to treat infections

Tigecycline, a new glycylcycline, is a theoretical option in

the treatment of infections caused by MR bacteria. It is

active against a variety of MR pathogens including MRSA

(MIC B 0.5 mg/L), VSE and VRE (MIC B 0.25 mg/L)

and ESBL and carbapenemase-producing Enterobacteria-

ceae (MIC B 1 mg/L) [50]. P. aeruginosa is resistant to

this antibiotic. However, recent studies show a lower effi-

cacy and a higher mortality of patients with severe infec-

tions treated with tigecycline compared to those receiving

control antibiotics [52]. More information is clearly needed

to make appropriate decisions about the usefulness of

tigecycline in the treatment of MR infections in cirrhosis.

Considering this point and as commented previously,

severe infections caused by ESBL-producing Enterobac-

teriaceae should be treated with carbapenems (doripenem

0.5 g/8 h IV, ertapenem 1 g/12–24 h IV, meropenem

0.5–1 g/6–8 h IV, or imipenem 0.5–1 g/6–8 h IV) [50].

Severe infections caused by P. aeruginosa should be treated

with the combination of two IV antibiotics that are active

against this pathogen (i.e., ceftazidime 1–2 g/8–12 h or me-

ropenem 0.5–1 g/6–8 h plus ciprofloxacin 400 mg/8–12 h).

Table 2 Suggested empirical antibiotic therapy for nosocomial bacterial infections in cirrhosis

Type of infection Recommended empirical antibioticsa

SBP, SBE, and spontaneous

bacteremia

Carbapenem (i.e., meropenem 1 g/8 h IV) ? a glycopeptide (vancomycin or teicoplanin IV) to cover

ESBL-producing Enterobacteriaceae, MRSA, and VSEb

Urinary infectionsc Uncomplicated infections: nitrofurantoin (50 mg/6 h PO) or fosfomycin (1 g/8 h PO)

Complicated infections (sepsis, severe sepsis, or shock): carbapenem ? glycopeptideb

Pneumoniac A carbapenem active against P. aeruginosa (i.e., meropenem 1–2 g/8 h IV) or ceftazidime

(2 g/8 h IV) ? ciprofloxacin (400 mg/8 h IV).

IV vancomycin or linezolid should be added in patients with risk factors for MRSAd

Cellulitis A carbapenem active against P. aeruginosa or ceftazidime ? a glycopeptideb

SBP spontaneous bacterial peritonitis; SBE spontaneous bacterial empyema; ESBL extended-spectrum b-lactamase; MRSA methicillin-resistant

S. aureus; VSE vancomycin-susceptible enterococci; VRE vancomycin-resistant enterococcia Empirical antibiotic therapy should be adapted to the local epidemiological patterns of resistant bacteriab In areas with a high prevalence of VRE, glycopeptides must be replaced by IV linezolid or daptomycinc Nosocomial and HCA infectionsd Ventilator-associated pneumonia, previous antibiotic therapy, nasal MRSA carriage

Hepatol Int (2013) 7:72–79 77

123

Some strains show an intermediate susceptibility to ceftazi-

dime, problem that can be solved through the continuous

infusion of this cephalosporin (6 g within 24 h after a loading

dose of 2 g IV). Severe infections caused by P. aeruginosa

resistant to b-lactams and carbapenems are extremely difficult

to treat. The combination of IV amikacin (MIC B 8 mg/L; IV

dose 15–20 mg/kg/day) and colistin (MIC B4 mg/L; IV dose

2–3 MU/8 h) is usually required. Risk of renal failure in this

setting is remarkable [50].

A glycopeptide (vancomycin 15–20 mg/kg/8–12 h or

teicoplanin 6 mg/kg) should be used in the treatment of

severe infections caused by VSE or MRSA. VRE infec-

tions should be treated with linezolid (600 mg/12 h IV) or

daptomycin (6–10 mg/kg/day). Daptomycin cannot be

used in the treatment of pneumonia because it is inhibited

by the pulmonary surfactant.

The treatment of carbapenemase-producing Entero-

bacteriaceae is even more difficult. Tigecycline is an

option, but doubts remain about its real clinical efficacy.

IV amikacin and colistin are also active against these MR

bacteria.

Conclusions

In conclusion, recent data demonstrate that currently rec-

ommended empirical antibiotic therapy (i.e., third-genera-

tion cephalosporins) is not appropriate for the treatment of

nosocomial infections in cirrhosis because of the high

prevalence of MR bacteria in this setting. New antibiotic

strategies for these infections should be tailored according

to the local epidemiological patterns of multiresistance. In

areas with a high prevalence of ESBL-producing Entero-

bacteriaceae, guidelines should include the use of carba-

penems. Glycopeptides, to cover MRSA and VSE, or

linezolid/daptomycin, to cover VRE, are also needed in the

empirical treatment of nosocomial infections in cirrhosis.

Acknowledgements FIS PI10/01373, Juan Acevedo was supported

by a grant from Instituto de Salud Carlos III (CM08/00129) and

Hospital Clinic. CIBEREHD is funded by the Instituto de Salud

Carlos III.

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