Haemophilus parainfluenzae Liver Abscess after Successful Liver Transplantation

Abstract

Haemophilus parainfluenzae was isolated from a bile specimen and from an aspirate of a liver abscess in a 58-year-old liver-transplanted woman that was indicative of an invasion of the graft by an ascending route. Drug therapy, immunosuppression, rejection therapy, and Roux-en-Y choledochojejunostomy may have contributed to the septic course. Interdisciplinary cooperation was instrumental in diagnosis and successful management in this case.

Infectious complications remain a major cause of morbidity and mortality after liver transplantation. The incidence of bacterial infections after liver transplantation differs considerably among transplantation centers, and reported infection rates range between 35 and 68% (1, 2, 8, 9, 12, 15). Patients under immunosuppressed conditions are at higher risk for infections and, in general, for infections which are caused by bacterial pathogens that are normally nonpathogenic. Herein we describe a patient who developed a nonbacteremic Haemophilus parainfluenzae liver abscess 1 year after successful orthotopic liver transplantation. H. parainfluenzae, a commensal organism of the upper respiratory tract, is an uncommon agent of human infection. It has been found to be associated with soft tissue infections, septic arthritis, genital tract infections, meningitis and brain abscesses (3), upper respiratory tract infections (10), endocarditis, bacteremia (7), and osteomyelitis (2). To date, only two cases of H. parainfluenzae liver abscess have been reported (3, 6).

Case report.

A 58-year-old woman was admitted to our hospital 1 year after liver transplantation for extrahepatic cholangiocarcinoma. She was suffering from recurrent fever attacks and cholestasis. The diagnosis of purulent cholangitis, choledocholithiasis, and common bile duct stenosis was made. Despite stenting of the bile duct stricture, the patient acquired multiple infections (recurrent cholangitis and urinary tract infection) with different bacterial strains, including Klebsiella oxytoca, Pseudomonas spp., Staphylococcus aureus (methicillin resistant), a coagulase-negative staphyloccocus, and Streptococcus faecium. Vancomycin and rifampin or ciprofloxacin were used for treatment. Three weeks after the last infection, liver enzyme levels increased and a liver biopsy was performed, revealing graft rejection. A steroid pulse was given, and the immunosuppressive regimen was switched from cyclosporine (CsA) to tacrolimus and azathioprine. Three days later, the patient had fever again and a blood culture yielded methicillin-resistant S. aureus and Streptococcus faecalis. Vancomycin was readministered for 1 week until a Roux-en-Y choledochojejunostomy was performed. Vancomycin was also used as an intraoperative as well as a perioperative agent in combination with metronidazole. Intraoperative bile samples were obtained, and H. parainfluenzae and Enterococcus faecalis were isolated. Two weeks after the Roux-en-Y choledochojejunostomy, the patient had recurrent fever attacks with negative blood cultures. An abdominal computed tomography scan was performed, showing a hypodense area in the eighth liver segment. A fine-needle aspiration was done, and an initial Gram stain of the aspirate showed gram-negative coccobacilli. Since the further testing identified the isolate as H. parainfluenzae, daily intravenous treatment with fleroxacin led to a favorable outcome. Three years after liver transplantation, the patient is well with normal graft function.

Discussion.

H. parainfluenzae is a commensal organism of the oropharynx and is present in over 20% of fecal samples analyzed (14). To date, only two cases of H. parainfluenzae biliary tract infections and only two H. parainfluenzae liver abscesses have been documented (Table 1). None of these infections was associated with bacteremia. This may indicate that H. parainfluenzae infection occurs via an ascending route. Two factors support this hypothesis. First, H. parainfluenzae grows well in the presence of V factor, which is abundant in the duodenum (11). Second, H. parainfluenzae bears iron-repressible outer membrane proteins closely related to those of enteric bacteria. These proteins may serve as adhesins, allowing colonization of the intestinal tract mucosa (13). Once H. parainfluenzae is established, it is provided with abundant V factor (NAD) excreted by the local flora.

TABLE 1.

Documented cases of H. parainfluenzae hepatobiliary tract infection

Clinical presentation	Case characteristica				Refer- ence
	Patient age	Underlying disease	Copathogen	Susceptibility profile
Hepatic abscess	26 yr	None	None	ND	6
	12 mo	CGD	None	Amps	3
	58 yr	Chol-CA	None	NR	This study
Biliary tract infection	65 yr	Gallstones	Streptococcus sanguis	ND	5
	56 yr	Chron. chol.	None	ND	4

^aAbbreviations: CGD, chronic granulomatous disease of childhood; Chol-CA, cholangiocellular carcinoma; Chron. chol., chronic cholecystitis; ND, not done; NR, no resistance. 

Our report strongly supports this hypothesis because an H. parainfluenzae liver abscess was evident after H. parainfluenzae was isolated from the common bile duct and blood cultures showed no concomitant bacteremia. There are some possible reasons why this ascending infection occurred. One is that the patient suffered from recurrent cholangitis with concomitant cholestasis, which allowed bacterial overgrowth. This overgrowth was supported by graft rejection therapy, switching of the immunosuppression therapy, and Roux-en-Y choledochojejunostomy.

Metronidazole is widely distributed. It appears in most body tissues, including bile, bone, liver, brain, breast milk, saliva, and seminal fluid, and achieves concentrations similar to those in plasma. Metronidazole is metabolized by side chain oxidation and glucuronide formation, and the majority of a dose of metronidazole is excreted in the urine, mainly as metabolites. Some of the metabolites also have antibacterial activity (16). Thus, metronidazole, in contrast to vancomycin, which is not excreted in bile, may have induced a change in the local bacterial flora. To prevent a further infection in that critical situation, we treated the patient with fleroxacin, although the susceptibility profile of the isolated strain indicated no resistance to any of the tested agents, including amoxicillin-clavulanic acid, aminopenicillin derivatives, tetracyclines, and expanded- and broad-spectrum cephalosporins.

It seems that the combination of the factors mentioned above was responsible for the rapid ascending progression from a localized infection of the common bile duct to a general condition of sepsis due to a liver abscess.