Inhibition of intracellular growth of Listeria monocytogenes by antibiotics

Abstract

We studied the activities of 15 antibiotics on the intracellular growth of Listeria monocytogenes in a HeLa cell line. After 24 h of contact with the infected cells, the antibiotics most effective against the intracellular growth of the 10 strains tested were amoxicillin, temafloxacin, and sparfloxacin, which nevertheless failed to totally eliminate the intracellular bacteria. Rifampin and co-trimoxazole had variable effects, depending on the isolates studied. The most active combinations were amoxicillin-sparfloxacin, co-trimoxazole-gentamicin, and sparfloxacin-co-trimoxazole. The results suggest the value of using a cell culture technique to study the activities of antibiotics against certain bacteria with intracellular sites of multiplication.

Comparative Intracellular (THP-1 Macrophage) and Extracellular Activities of β-Lactams, Azithromycin, Gentamicin, and Fluoroquinolones against Listeria monocytogenes at Clinically Relevant Concentrations

“…The model was further validated with respect to the main parameters that may govern intracellular activity (49), namely, the intrinsic antibacterial activities of the drugs under study (i.e., their MICs and MBCs), the rates of killing, and their levels of intracellular accumulation. All values or properties were consistent with previously published data (13,30,31,35,42) or are in line with the known properties of the corresponding drugs. a The cells were incubated in the presence of the maximum extracellular concentrations tested in this study (ampicillin, 50 mg/liter; meropenem, 50 mg/ liter; ciprofloxacin, 4.3 mg/liter; moxifloxacin, 4 mg/liter), and the levels of accumulation were determined after 5 h of incubation.…”

“…The disappointing behaviors of ampicillin and meropenem raise critical questions concerning the high rate of use of these antibiotics to treat severe cases of listeriosis and point out their probable inabilities to rapidly achieve bacterial eradication in immunocompromised patients. A poor effect of amoxicillin (0.5-log reduction of intracellular L. monocytogenes) has been described in a HeLa cell model at the 5-h time point (31). A progression of the decline in bacterial counts (reductions up to ϳ2 logs) was recorded, however, when incubation with the antibiotic was continued up to 24 h. This pattern is consistent with the known time dependency of ␤-lactam activities.…”

“…Several investigators have reported that fluoroquinolones are capable of killing intracellular L. monocytogenes (13,30,31,34,42). These studies showed that the fluoroquinolones had activities that were inversely proportional to their MICs and directly proportional to the C e .…”

“…These observations may suggest the absence of a true correlation between the cellular accumulation of antibiotics in cell models and their effective in vivo intracellular activities (perhaps because of modulation by a series of critical parameters such as subcellular drug bioavailability and intracellular expression of activity (30,31,49). Yet, it is also possible that the macrolides and fluoroquinolones that have been examined so far exhibit intrinsic activities that are too weak (i.e., have MICs that are too high, as determined for extracellular bacteria) and therefore cannot be used in vivo at concentrations that are high enough.…”

Intracellular pharmacodynamics of antibiotics

“…One is struck, however, by the impairment of activity, which may make fluoroquinolones ineffective unless a sufficiently high extracellular concentration can be reached. This limitation was already underlined for Listeria [88,89], and may be critical for S aureus if considering methicillin- Fig. 4.…”