Levofloxacin versus ciprofloxacin, flucloxacillin, or vancomycin for treatment of experimental endocarditis due to methicillin-susceptible or -resistant Staphylococcus aureus

Abstract

Levofloxacin is the L isomer of ofloxacin, a racemic mixture in which the L stereochemical form carries the antimicrobial activity. Levofloxacin is more active than former quinolones against gram-positive bacteria, making it potentially useful against such pathogens. In this study, levofloxacin was compared to ciprofloxacin, flucloxacillin, and vancomycin for the treatment of experimental endocarditis due to two methicillin-susceptible Staphylococcus aureus (MSSA) and two methicillin-resistant S. aureus (MRSA) isolates. The four test organisms were susceptible to ciprofloxacin, the levofloxacin MICs for the organisms were low (0.12 to 0.25 mg/liter), and the organisms were killed in vitro by drug concentrations simulating both the peak and trough levels achieved in human serum (5 and 0.5 mg/liter, respectively) during levofloxacin therapy. Rats with aortic endocarditis were treated for 3 days. Antibiotics were injected with a programmable pump to simulate the kinetics of either levofloxacin (350 mg orally once a day), ciprofloxacin (750 mg orally twice a day), flucloxacillin (2 g intravenously four times a day), or vancomycin (1 g intravenously twice a day). Levofloxacin tended to be superior to ciprofloxacin in therapeutic experiments (P = 0.08). More importantly, levofloxacin did not select for resistance in the animals, in contrast to ciprofloxacin. The lower propensity of levofloxacin than ciprofloxacin to select for quinolone resistance was also clearly demonstrated in vitro. Finally, the effectiveness of this simulation of oral levofloxacin therapy was at least equivalent to that of standard treatment for MSSA or MRSA endocarditis with either flucloxacillin or vancomycin. This is noteworthy, because oral antibiotics are not expected to succeed in the treatment of severe staphylococcal infections. These good results obtained with animals suggest that levofloxacin might deserve consideration for further study in the treatment of infections due to ciprofloxacin-susceptible staphylococci in humans.

Synergistic interaction between phage therapy and antibiotics clears Pseudomonas aeruginosa infection in endocarditis and reduces virulence

“…No significant difference between the 2 routes of administration was observed. Notably, a single bolus injection of ciprofloxacin simulating a single oral dose of 750 mg in adults [17] decreased median vegetation bacterial titers by 2.6 log CFUs/g (Figure 3B), which was comparable with phage therapy. Moreover, the combination of phages with ciprofloxacin was highly synergistic, resulting in negative vegetation cultures in 7 of 11 rats receiving combined therapy after 6 hours, as compared with 0 of 28 in phage-alone or ciprofloxacin-alone treated groups (Figure 3B) ( P < .005).…”

“…Experiments were performed under license number 879.9 and in accordance with the regulations of the cantonal committee on animal experimentation of the State of Vaud, Switzerland. The production of catheter-induced aortic vegetations and the installation of an intravenous line into the superior vena cava, connected to an infusion pump to deliver the phage cocktail, were performed in female Wistar rats as previously described [17]. Details are provided in the Supplementary Materials.…”

De novo designed synthetic mimics of antimicrobial peptides

“…As a control, parallel cultures were also exposed to 0.5× MIC concentrations of ciprofloxacin or norfloxacin, two broad spectrum fluoroquinolones for which resistance has been reported in this experimental format. [67] There is no change in the MICs for PMX70004, PMX10072 or PMX10066 over the entire 17 passage time course. Conversely, an increase in the MIC is readily observed by passage seven for both ciprofloxacin and norfloxacin.…”

Oral antibiotic therapy for the treatment of infective endocarditis: a systematic review

“…Newer fluoroquinolones such as levofloxacin and moxifloxacin also have favourable pharmacologic profile when given orally and are bactericidal against S. aureus, and in contrast to ciprofloxacin, the development of in-vivo resistance appears rare [27,33,34]. Both levofloxacin and moxifloxacin have also proved effective in animal models of infective endocarditis [35,36] and in anecdotal human cases [37,38]. Therefore, it would also be reasonable to consider the oral formulations of these drugs in future studies for the treatment of this infection.…”