We created an infection model and observed the effect of the antibacterial action of Levofloxacin on the airways mucosa.
We injected the influenza virus, then Streptococcus pneumoniae on day 3.
Levofloxacin was administered for four days starting two hours after the dose of Streptococcus pneumoniae. On day 10 of the infection, the results were compared with those in an untreated group.
First of all, the subject was infected with the influenza virus through the nose.
What we see is the respiratory tract directly above the bronchial bifurcation.
In a normal respiratory tract, the motion of the cilia is quite brisk.
When we focus on the lamina propria mucosae, we can see the mucus flow. The mucus, which has picked up tiny particles and bacteria, is designed to protect against infection by means of ciliary motion that removes the source of infection.
Day 3 of the influenza virus infection.
The mucous membrane of the respiratory tract is severely damaged and we can see almost no ciliary motion.
The desquamated cells are visible.
The remaining cilia are short and barely move.
On day 3 after the virus administration, a dose of Streptococcus pneumoniae was given to mice infected with the influenza virus.
By day 4 following the added dose of Streptococcus pneumoniae, two of the six mice have already died.
The respiratory tracts of the surviving mice. Virtually no cilia can be seen and there is no motion.
The truncated cilia exhibit only slight movement.
Now we focus on the lamina propria mucosae.
We can see numerous neutrophils that have entered the spaces between the fibers of connective tissue.
On day 10 an additional dose of Streptococcus pneumoniae was administered.
In the untreated group, some short cilia can be seen, but the cilia exhibit only slight movement.
We can see ciliary motion on the right-hand side facing the screen. In the central area the mucus layer is thick, and we cannot see any cilia.
If we focus on the mucus layer, we see that many neutrophils are gathering in the mucus.
When we enlarge the view, we can also see the Streptococcus pneumoniae.
If we use time-lapse filming to speed the time up, we can see that neutrophils have gathered and are encapsulating the bacteria. This becomes the purulent sputum that accompanies bacterial infections.
Even in the areas where ciliary motion persists, if we focus on the lamina propria mucosae, we can see a comparatively large number of neutrophils.
This is the group receiving Levofloxacin. Oral doses of Levofloxacin equivalent to once-daily 500-mg clinical doses were administered to mice. These were given every day for four days starting two hours after the additional dose of Streptococcus pneumoniae.
On day 10 of the additional dose of Streptococcus pneumoniae, all the mice in the Levofloxacin-dosed group were still alive.
This is a respiratory tract from the Levofloxacin-treated group.
The long cilia are performing a rippling action and exhibit a vigorous swirling motion.
In the Levofloxacin-treated group, the Streptococcus pneumoniae is already undetectable.
Even if we focus on the lamina propria mucosae, there are only connective fibers and we can scarcely see the neutrophil permeation.
We now confirm the situation by scanning electron microscopy. The mucous membrane of the respiratory tract is normal.
When the influenza virus infects the tract, the cilia are desquamated. The mucous membrane of the respiratory tract is damaged,
and the tract is susceptible to a bacterial secondary infection.
On the right-hand side is the Levofloxacin-treated group.
Thanks to the administration of Levofloxacin in amounts equivalent to once-daily 500-mg clinical doses, the Streptococcus pneumoniae in the infection model fell below the detection threshold in the trachea, and were also below that threshold in the lungs.
On day 10 of the additional dose of Streptococcus pneumoniae, the respiratory tract cilia had already recovered in the Levofloxacin-treated group.
In secondary bacterial infectious disease arising from influenza, prompt administration of Levofloxacin is effective.