Listeria monocytogenes-associated biliary tract infections: a study of 12 consecutive cases and review

Abstract

At present, little is known regarding Listeria monocytogenes-associated biliary tract infection, a rare form of listeriosis.In this article, we will study 12 culture-proven cases reported to the French National Reference Center for Listeria from 1996 to 2013 and review the 8 previously published cases.Twenty cases were studied: 17 cholecystitis, 2 cholangitis, and 1 biliary cyst infection. Half were men with a median age of 69 years (32-85). Comorbidities were present in 80%, including cirrhosis, rheumatoid arthritis, and diabetes. Five patients received immunosuppressive therapy, including corticosteroids and anti-tumor necrosis factor biotherapies. Half were afebrile. Blood cultures were positive in 60% (3/5). Gallbladder histological lesions were analyzed in 3 patients and evidenced acute, chronic, or necrotic exacerbation of chronic infection. Genoserogroup of the 12 available strains were IVb (n=6), IIb (n=5), and IIa (n=1). Their survival in the bile was not enhanced when compared with isolates from other listeriosis cases. Adverse outcome was reported in 33% (5/15): 3 deaths, 1 recurrence; 75% of the patients with adverse outcome received inadequate antimicrobial therapy (P=0.033).Biliary tract listeriosis is a severe infection associated with high mortality in patients not treated with appropriate therapy. This study provides medical relevance to in vitro and animal studies that had shown Listeria monocytogenes ability to survive in bile and induce overt biliary infections.

FIGURE 1

Multilocus sequence typing-based minimum spanning tree of 745 Listeria monocytogenes isolates of lineages I and II. Each circle denotes a single type (ST) and the diameter reflects the number of isolates in that ST. Red sectors denote biliary-tract infections isolates; white sectors correspond to other isolates. Bold lines between circles correspond to links with a single allelic mismatch; plain lines correspond to those with 2 allelic mismatches. Links corresponding to more than 2 allelic mismatches are not represented, as several equally likely alternative links exist; therefore, the relative positions of clonal complexes (CCs) or single STs should not be taken as evidence of phylogenetic proximity. Values inside circles indicate the ST numbers of the central STs of numerically important CCs. Left panel represents lineage I whereas right panel represents lineage II. The arrow denotes 2 isolates from the same patient (Patient 2) who presented with a documented recurrence of infection. All data are available at http://www.pasteur.fr/mlst.

FIGURE 2

Bile resistance in 10 French isolates and in 30 strains selected at random among isolates received in 2012 from the National Reference Center for Listeria from patients with septicemia (S), central nervous system (CNS), and maternal–neonatal (MN) infections. The minimal inhibitory concentration of bile for a strain was interpreted as the lowest concentration totally inhibiting the growth of spots. P values were determined as compared to S, CNS, and MN isolates (Mann–Whitney test). BTI = bile tract infections.

FIGURE 3

Biofilm formation in 12 French isolates and in 30 strains selected at random among isolates received in 2012 from the National Reference Center for Listeria from patients with septicemia (S), central nervous system (CNS), and maternal–neonatal (MN) infections. P values were determined as compared to S, CNS, and MN isolates (Mann–Whitney test). BHI =  brain heart infusion, BTI = bile tract infections.

FIGURE 4

(A–C) Gallbladder sections from 3 patients with acute cholecystitis (Patient 1), (D–F) necrotic exacerbation of chronic cholecystitis (Patient 2), and (G–I) chronic cholecystitis (Patient 3). Lm was genoserotyped as IVb in the 3 cases. In acute cholecystitis, HE staining revealed edematous congestive transmural inflammation (A; arrow), polymorphonuclear cells infiltrate (B; arrow), and focal mucosal ulceration (B; arrowhead). Lm was seen in the lumen as aggregates and individual bacteria (C). In the necrotic exacerbation of chronic infection, necrosis involved the mucosa and the muscularis (D, E), with necrotic luminal tissue debris and inflammatory fibrosis in the serosal coat. Lm was located in the lumen and in necrotic tissues lining the lumen (F). In chronic cholecystitis, diffuse mucosal-based infiltrate of mononucleate cells was observed (G, H; arrow). Lm was observed inside the lumen (I). Scale bars: HE staining, 100 µm; IHC staining, 2 µm. HE = hematoxylin–eosin, IHC = immunohistochemistry, L = lumen, P = peritoneal cavity.