Impact of multidrug resistance on the management of bacterial infections in cirrhosis

Table 1 Prevalence and prognosis of multidrug-resistant organisms infections in cirrhosis

Ref.	Study design	n	MDR infection (%)	Mortality (%)	Comments
Piano et al[7]	Single center study	75	35.0	86.0	ACLF grade 2 and 3 were more frequent in MDRO infected patients
Cassini et al[3]	Meta-analysis	671 689	NA	4.9	Estimate the incidence of infections caused by selected antibiotic-resistant bactéria in countries of the EU and EEA in 2015
Trebicka et al[9]	European multicenter	376	18.9	40.8 at 28.0 d; 48.7 at 90.0 d	In infection-induced ACLF, the prevalence of MDR strains was significantly higher; severe sepsis (40.7% vs 21.6%), ACLF (72.3% vs 42.0%) and 90-d mortality (48.7% vs 30.7%) were more frequent in infections caused by MDR strains compared to non-MDR strains
Costabeber et al[17]	Retrospective	474	37.5	-	To evaluate the resistance profile of bacteria isolated from cirrhotic patients admitted to a referral hospital in Brazil
Trebicka et al[9]	European multicenter	520	14.8	35.1 at 28.0 d	MDROs were not significantly different between specific infections in the different European regions; MDROs were more frequently isolated in the ICU (23.8% vs 12.2%) and nosocomial infections (21.3% vs 8.3% and 6.6% in CA and HCA infections, respectively); MDROs were more prevalent in infections causing severe sepsis/shock (30.3% vs 12.2%) or ACLF (20.5% vs 9.4%)
Johnson et al[18]	Retrospective	3951	5.6	27.7	Presence of MDR bacteria in the blood was not associated with in-hospital mortality

ACLF: Acute on chronic liver failure; EU: European Union; EEA: European Economic Area; MDR: Multi-drug resistant; MDRO: Multi drug resistant organism; ICU: Intensive care unit; CA: Community acquired; HCA: Health-care associated; NA: Not available.

Table 2 Risk factors for multidrug-resistant infection in cirrhosis

No.	Risk factors for MDR infection in cirrhosis
1	Prior (3 mo) use of broad-spectrum antibiotics
2	Prior infection by MDROs (6 mo)
3	Nosocomial infection
4	Recent contact with the healthcare system
5	Site of infection (pneumonia, skin, and soft tissue infections)
6	Geographic region
7	Prophylactic use of antibiotics (?)/proton pump inhibitors use?

MDR: Multi-drug resistant; MDRO: Multi drug resistant organism.

Table 3 Recommended empirical antibiotic treatment for bacterial infection in cirrhosis

Type of infection	Community-acquired infection	Nosocomial and HCA infection or sepsis
SBP, spontaneous bacterial empyema and spontaneous bacteremia	Cefotaxime or Amoxicilin/clavulanic acid	Piperacillin/tazobactam or Meropenem ± Vancomycin or Daptomycin or Linezolid1
UTI	Fosfomycin or cotrimoxazole	Uncomplicated: Nitrofurantoin or Fosfomycin; if sepsis: Piperacillin/tazobactam or Meropenem ± Glycopeptide
Pneumonia	Amoxicilin/clavulanic acid; Ceftriaxone + Macrolide; Levofloxacin; Moxifloxacin	Piperacillin/tazobactam or Meropenem or Ceftazidime + Ciprofloxacin; Glycopeptides or Linezolid1 should be added in patients with risk factors for MRSA2
Skin and soft tissue infections	Amoxicilin/clavulanic acidor ± Clindamycin	Meropenem or Piperacillin/tazobactam + Glycopeptide or Daptomycin or Linezolid1 ± Cindamycin; if necrotizing fascitis: Meropenem + Daptomycin + Clindamycin

¹Vancomycin, teicoplanin or daptomycin in areas with a high prevalence Methicillin-resistant Staphylococcus aureus and vancomycin-susceptible enterococci. Vancomycin must be replaced by linezolid in areas with a high prevalence of vancomycin-resistant enterococci.

²Ventilator-associated pneumonia, previous antibiotic therapy, nasal Methicillin-resistant Staphylococcus aureus carriage.

HCA: Health care associated; MRSA: Methicillin-resistant Staphylococcus aureus; SBP: Spontaneous bacterial peritonitis; UTI: Urinary tract infection.