Infections in liver transplant recipients

Table 1 Selected infections after liver transplantation

Time period after liver transplantation
1st mo	Between 1st and 6th mo	Beyond 6th mo
General risks: surgical procedure, prolonged hospitalization, prior colonization, mechanical ventilation, indwelling vascular and urinary catheterization, donor-transmitted diseases, among others	General risks: over-immunosuppression, D+/R- mismatch status for viruses, allograft rejection, donor-transmitted diseases, repeated biliary tract manipulations, re-transplantation	General risks: variable
		High-risk patients include those with recurrent rejection and allograft dysfunction that would require intense immunosuppression
Bacterial infections including resistant pathogens – bloodstream infections, pneumonia, surgical site infections, intra-abdominal infections, abscesses, urosepsis, Clostridium difficile associated colitis	Bacterial infections continue to occur in some patients – bloodstream infections, pneumonia, abdominal infections, C difficile associated colitis	Minimal immunosuppression – usual community acquired infections and zoster
Herpes simplex virus infection – herpes labialis or genitalis with potential for disseminated disease	Opportunistic pathogens: cytomegalovirus, Epstein-Barr virus, human herpesvirus 6 and 7, Aspergillus species, Pneumocystis jirovecii, Nocardia species, Mycobacterium tuberculosis, endemic mycoses, Toxoplasma gondii, among others	Intense immunosuppression due to allograft rejection and dysfunction – infections occurring during the opportunistic period (see middle column) continue to occur; course of chronic viral hepatitis may be accelerated
Candida sp. infections – fungemia, abscesses, urosepsis

Table 2 Suggested prevention and treatment regimens for various infections after liver transplantation

Infection	Prevention	Treatment
Bacterial infections	According to risk factors (i.e. cephalosporins or vancomycin)	Susceptibility-guided antimicrobial treatment
Herpes simplex virus	Acyclovir 400 mg PO BID for 4 wk (if they are not receiving drugs for CMV prevention)	Acyclovir 5 mg/kg every 8 h for mucocutaneous disease or 10 mg/kg every 8 h for encephalitis
		Valacyclovir 1 gram PO BID for less severe disease
Cytomegalovirus	Valganciclovir 900 mg daily for 3-6 mo	Valganciclovir PO 900 mg BID or ganciclovir IV 5 mg/kg BID.
	Oral ganciclovir, 1 gram TID for 3-6 mo	If severe or life-threatening disease, initiate therapy with IV ganciclovir.
	Preemptive therapy (guided by CMV PCR or antigenemia)	Treatment must continue until viral eradication is achieved, but not shorter than 2 wk
		CMV Ig may be considered for severe forms of disease like pneumonitis.
Varicella zoster virus	Pre-transplant vaccination	Valacyclovir 1-gram PO TID or IV acyclovir 10 mg/kg every 8 h
		Initiate with IV acyclovir for disseminated disease such as pneumonia or encephalitis
		VZV immunoglobulin adds no additional benefits and not recommended
Candida species	Fluconazole, echinocandin, or amphotericin B in high-risk recipients for 4 weeks	Amphotericin B 3 to 5 mg/kg IV daily
		Fluconazole 800 mg loading dose, then 400 mg PO daily
		Caspofungin at an initial dose of 70 mg followed by 50 mg daily
		Anidulafungin initial dose of 200 mg first day followed by 100 mg daily
Aspergillus species	Voriconazole, echinocandin, or amphotericin B in high-risk patients	Voriconazole 6 mg/kg IV BID on day 1 followed by 4 mg/kg BID daily; transition to oral regimen when clinically stable
		Echinocandins (caspofungin or anidulafungin)
		Amphotericin B preparations
Cryptococcus neoformans	Not recommended	Amphotericin B (conventional or liposomal) and flucytosine (5-FC) for at least 2 wk then fluconazole as long-term maintenance (e.g. 6 mo)
		Fluconazole 800 mg loading dose, then 400 mg PO daily for limited disease
Pneumocystis jirovecii	TMP- SMX 160/800 mg daily or three times per week	TMP- SMX preferred; 15-20 mg/kg per day of TMP component in 3-4 divided doses (keep the sulfa level above 100); transition to oral regimen when clinically stable
	Alternative: TMP-SMX 80/400 mg daily
		Alternatives: Pentamidine isethionate, trimethoprim-dapsone (in patients who are not deficient in glucose-6-phosphate dehydrogenase), atovaquone, and clindamycin-primaquine.
Toxoplasma gondii	TMP- SMX 160/800 mg daily	Pyrimethamine in combination with sulfadiazine or clindamycin.
Listeria monocytogenes	Not recommended but TMP- SMX for Pneumocystis prophylaxis may prevent some infections	Ampicillin 2 g IV every four hours plus Gentamicin 3 mg/kg per day IV in three divided doses
		Alternatives:
		TMP- SMX 10-20 mg/kg IV per day divided every 6 to 12 h
		Meropenem 2 g IV every eight hours
Nocardia asteroides	Not recommended but TMP- SMX for Pneumocystis prophylaxis may prevent some infections	TMP-SMX preferred; 8-10 mg/kg per day of TMP component in 2-4 divided doses; higher doses may be used in severe disease; transition to oral therapy when clinically stable

CMV: cytomegalovirus; VZV: Varicella zoster virus; HSV: herpes simplex virus; TMP–SMX: trimethoprim sulfamethoxazole.

Table 3 Risk factors of fungal infections after liver transplantation

Candida species	Aspergillus species
Renal insufficiency	Renal insufficiency
Renal insufficiency (creatinine > 3.0 mg/dL)	Renal failure
Renal replacement therapy within the first 30 days after transplant	Need for dialysis
Surgical factors	Surgical factors
Prolonged transplant operation time (> 11 h)	Retransplantation
Second surgical intervention for any reason within 5 d of the initial transplant procedure	Microbial factors
Choledochojejunostomy anastomosis.	CMV infection
Transfusion of ≥ 40 units of blood products during the surgery	Prior colonization
Microbial factors	Fulminant hepatic failure
Early fungal colonization (within 3 d after liver transplantation)
Documented colonization (nasal, pharyngeal or rectal cultures)
Fulminant hepatic failure

CMV: cytomegalovirus.