Management of bacterial and fungal infections in end stage liver disease and liver transplantation: Current options and future directions

Table 4 Treatment options for multidrug resistant organisms in liver transplant recipients

Pathogens	Recommendation	Antimicrobial regimens	Ref.
MDR Gram-positives
MRSA	Nasal decolonization with mupirocin. Daptomycin highly bactericidal in BSI; non effective in pulmonary infections. Linezolid and tigecycline bacteriostatic.	Vancomycin1/linezolid OR Daptomycin OR Tigecycline OR Novel anti-MRSA cephalosporins (ceftaroline, ceftobiprole)2.	[107-111]
VRE	Daptomycin highly bactericidal in BSI; non effective in pulmonary infections. Linezolid and tigecycline bacteriostatic.	Linezolid OR Daptomycin OR Tigecycline.	[113,121,122]
MDR Gram-negatives
ESBL-producing Enterobacteriaceae	Conflicting data on carbapenem superiority vs BLBLI. Meropenem recommended for high inoculum infections and unstable patients.	Carbapenems OR Piperacillin/tazobactam.	[175-177]
Carbapenem-resistant Enterobacteriaceae	Test antimicrobial susceptibility (also on colonizing strains). Some evidence of better outcomes with combination therapy vs monotherapy. New molecules promising but scarce data in LT.	Ceftazidime/avibactam, OR Combination regimen (at least two active drugs) including colistin/polymixin B, tigecycline, aminoglycosides1 (gentamycin, amikacin), IV fosfomycin, high-dose prolonged infusion carbapenems. For uncomplicated UTI, consider monotherapy (aminoglycosides, fosfomycin).	[127,137,138,175,178]
MDR P. aeruginosa	Test antimicrobial susceptibility. New molecules promising but scarce data in LT.	Combination regimen (at least two active drugs) including colistin, an anti-pseudomonal beta-lactam (if susceptible), aminoglycosides1, fosfomycin OR Ceftolozane/tazobactam, ceftazidime/avibactam	[175,179,180]

¹Therapeutic drug monitoring recommended;

²Approved for skin and soft tissue infections and community-acquired pneumonia (ceftaroline), community-acquired and hospital-acquired pneumonia excluding ventilator-associated pneumonia (ceftobiprole). MDR: Multidrug resistant; BLBLI: Beta-lactam/beta-lactamase inhibitor combination; BSI: Bloodstream infections; LT: Liver transplantation; MDRO: Multidrug-resistant organisms; MRSA: Methicillin-resistant Staphylococcus aureus; VRE: Vancomycin-resistant enterococci; CRE: Carbapenem-resistant Enterobacteriaceae.