Listeria monocytogenes endocarditis: case report, review of the literature, and laboratory evaluation of potential novel antibiotic synergies

Abstract

Endocarditis is a rare but serious manifestation of Listeria monocytogenes (LM). However, the optimal treatment strategy for LM endocarditis has yet to be established. Current antibiotic strategies for listeriosis include penicillin G or ampicillin (AMP) monotherapy, or AMP + gentamicin combination therapy which is often favored for endocarditis. The primary objective of our investigation was to assess the utility of AMP + ceftriaxone (CRO) and AMP + daptomycin (DAP) against LM, modeling less nephrotoxic antibiotic combinations traditionally used to manage resistant enterococcal endocarditis. Here we report a case of LM endocarditis, review the world literature, and evaluate alternative treatment strategies for listeriosis utilizing in vitro and ex vivo studies. The combination of AMP + CRO and AMP + DAP were each noted to have synergistic activity against a LM endocarditis isolate. Additionally, co-incubation of the isolate with sub-lethal concentrations of antibiotics (AMP, CRO, DAP, AMP + CRO or AMP + DAP) sensitized the bacterium to whole blood killing while pretreatment with CRO and DAP (at 1/4 MIC) sensitized the bacterium to neutrophil killing. However, these effects did not reflect potentiation of antibiotic activity to human cathelicidin peptide LL-37, which is abundant in neutrophils and highly active against LM. Interestingly, AMP pretreatment of the LM endocarditis isolate resulted in increased DAP binding to the bacterium when assessed by fluorescence microscopy. These in vitro and ex vivo studies suggest further investigation of combination therapy using AMP + CRO or AMP + DAP as an alternative treatment for LM infection is warranted.

Listeria Bacteremia Presenting With Cerebral Abscess and Endocarditis in an Elderly Patient With Chronic Immune Thrombocytopenia

“…It is ubiquitous in nature with a broad host range. The bacterium has been isolated from soil, vegetation, and as part of the fecal flora in many mammals [1,[3][4][5][6]. It is also normally found in the stools of 1-5% healthy adults [7,8].…”

“…From 1968 to 2017, only 73 cases of listerial brain abscess were reported in the literature, with a case fatality rate of 27.3% [5]. Furthermore, endocarditis due to Listeria monocytogenes is a rare entity occurring in only about 5-8% of patients with listeriosis [2,4,13]. A review of the literature from 1955 to 2008 found only 68 case reports of listerial endocarditis [14], with a case fatality rate ranging from 37-50% [4,6].…”

“…Listeria monocytogenes is transmitted through consumption of contaminated foods including processed/delicatessen meats, soft cheeses, pâtés, vegetables, ice creams, unpasteurized milk, raw or ready-to-eat seafood, vegetables, and fruits such as cantaloupe [ 1 , 3 , 4 ]. It can grow over a wide variety of temperatures.…”

“…It is more motile at lower temperatures between -2°C (28.4°F) and -42°C (-43.6°F), compared to a normal body temperature of 37°C (98.6°F) [ 1 , 3 , 9 ]. The bacterium can withstand harsh temperatures and low pH environments, thereby resisting killing by several food processing technologies [ 3 , 4 , 9 ]. It is weakly β-hemolytic on blood agar and is diagnosed through the culture of body fluids (specifically blood, cerebrospinal fluid, amniotic fluid) or brain tissue [ 1 , 10 ].…”

“…Furthermore, endocarditis due to Listeria monocytogenes is a rare entity occurring in only about 5-8% of patients with listeriosis [ 2 , 4 , 13 ]. A review of the literature from 1955 to 2008 found only 68 case reports of listerial endocarditis [ 14 ], with a case fatality rate ranging from 37-50% [ 4 , 6 ].…”