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.