Comparative activities of new fluoroquinolones, alone or in combination with amoxicillin, trimethoprim-sulfamethoxazole, or rifampin, against intracellular Listeria monocytogenes

Abstract

We studied the activities of the new fluoroquinolones clinafloxacin, levofloxacin, ofloxacin, and sparfloxacin alone or in combination on the intracellular growth of Listeria monocytogenes. Against intracellular growth of the four strains tested, a similar reduction of the bacterial count was obtained with clinafloxacin at the dose of 10 x MIC (delta log10 CFU/ml = -2.19 +/- 0.24), with levofloxacin at 8 x MIC (delta log10 CFU/ml = -2.28 +/- 0.25), and with sparfloxacin at 4 x MIC (delta log10 CFU/ml = -2.16 +/- 0.21) after 24 h of incubation. The combination of the quinolones with trimethoprim-sulfamethoxazole or amoxicillin did not show a substantial increase in activity compared to the fluoroquinolone alone. Antagonism with rifampin was strongly suggested. No modification of the MIC was observed after 20 successive infections of HeLa cells and contact with subinhibitory concentrations of clinafloxacin, levofloxacin, and sparfloxacin for 24 h. We conclude that clinafloxacin, levofloxacin, or sparfloxacin could represent a therapeutic alternative to amoxicillin for the treatment of Listeria infections in adults, especially clinafloxacin, whose MIC is low (0.06 to 0.12 micrograms/ml), and whose best activity against intracellular L. monocytogenes was obtained at a concentration of 1.2 micrograms/ml, which is similar to clinically achievable levels. The results must be confirmed in an experimental model.

An update on the medical management of listeriosis

“…As rifampicin penetrates well into the host cells and is active against intracellular Listeriae [43], it has been used in animal experiments as an additional drug to ampicillin and gentamicin [31]. As a result of the convincing experimental evidence showing that this triple combination exerts a high cure rate, it has also been proposed for clinical cases.…”

“…It is accumulated within host cells, but its inhibiting effect on intracellular bacteria is minor compared to ampicillin [31]. Cotrimoxazole easily finds access to many organs, including the CNS [39].…”

“…As L. monocytogenes is a facultative intracellular pathogen, the activity of antimicrobials has to be evaluated not only in vitro (i.e., on extracellular bacteria in artificial media), but also in cell cultures [31] and even in animal experiments imitating systemic listeriosis [32] or meningitis [33].…”

Fluoroquinolones in the treatment of meningitis

“…In this experimental setting, clinafloxacin was the most active compound. The minimal bactericidal concentration (MBC)/MIC ratio was less than two for all the tested fluoroquinolones [41]. In an earlier study using the same system, the bactericidal activity of ciprofloxacin, lomefloxacin, ofloxacin, sparfloxacin, and temafloxacin were compared.…”

Sir Thomas Sydenham Revisited

“…Rifampin is also highly active in vitro and, although not synergistic, may be additive in its effect; therefore, a combination of rifampin and TMP-SMZ would be worth consideration for the treatment of a patient who is allergic to penicillin. Although in vitro antagonism between ampicillin and rifampin has been demonstrated [3,4], the combination is active in in vitro models of infection. An excellent review of antibiotic treatment of listeriosis recently has been published by Hof et al [5].…”