Transcript Prophylactic Effectiveness of 2 Fluoroquinolones on Staphylococcus

The Prophylactic Effectiveness
of Two Fluoroquinolones on
Staphylococcus aureus in
Rabbit Eyes
Balzli C, Caballero A, Tang A, Weeks A,
O’Callaghan R
University of Mississippi Medical Center, Microbiology
Department, Jackson, MS
The authors of this poster have received research funding and travel
expenses from Alcon Laboratories Inc.
Introduction
 Staphylococcus aureus represents a significant


infectious agent causing keratitis and
endophthalmitis associated with penetrating
surgery (i.e. cataract surgery).
S. aureus, particularly methicillin-resistant S.
aureus (MRSA), infections can be very
damaging to the eye and is increasingly difficult
to treat.
Topical fluoroquinolones are commonly used
prophylactically and as treatment for such
infections due to their spectrum of coverage
and overall activity, as well as their ability to
penetrate tissues.
Introduction
 The effectiveness of fluoroquinolones has been
demonstrated many times in experimental MRSA
keratitis models.
 In the past, gauging the bactericidal effectiveness of
these drugs on S. aureus in the anterior chamber has
relied on in vitro data such as drug concentrations in
the aqueous humor and minimum inhibitory
concentrations (MIC) because S. aureus typically
dies within the rabbit anterior chamber.
 In these studies, a clinical isolate of MRSA was found
to grow in the anterior chamber and was used to
quantify the prophylactic bactericidal effectiveness of
moxifloxacin and besifloxacin, a new fluoroquinolone,
in the rabbit cornea and anterior chamber.
Growth of MRSA659 in the
Anterior Chamber
LogCFU/ml
USA300 – Community Acquired MRSA (Strain NRS659*)
7
6
5
4
3
2
1
0.5
2
4
6
Hours Post-Infection
106 CFU inoculum : n ≥ 3 / time point
* Network on Antimicrobial Resistance in S. aureus
8
10
10hr PI
MRSA659 Susceptibility to
Fluoroquinolones
 MICs of the commercial ophthalmic formulations
of moxifloxacin (0.5%) and besifloxacin (0.6%)
were determined.
moxifloxacin
0.06 µg/ml
n=6
besifloxacin
0.03 µg/ml
 After determining the growth and susceptibility
of MRSA659, the prophylactic effectiveness of
the two fluoroquinolones were tested in keratitis
and endophthalmitis infection models in the
rabbit eye.
Prophylactic Treatment
Topical application
of drug (45 µl)
30 min
Rinse eye
with PBS
Infect cornea or
anterior chamber
30 min
Quantify CFU of
anterior chamber
Treatment Groups:
0.6% besifloxacin (Besivance) 45 µl
0.5% moxifloxacin (Vigamox) 45 µl
Untreated
30 Minute Prophylaxis
of MRSA Keratitis
Inoculation = 106 CFU : n = 4/group
Log CFU/Cornea
6
5
*
4
3
4.01
± 0.22
5.72
± 0.21
5.98
± 0.05
Moxifloxacin
Besifloxacin
Untreated
2
than besifloxacin treated or
* - Fewer CFU/cornea
untreated corneas (P ≤ 0.0023)
Log CFU/ml Aqueous
30 Minute Prophylaxis of
MRSA Endophthalmitis
Inoculation = 106 CFU : n = 8/group
6
5
*
4
3
3.30
± 0.12
5.01
± 0.14
4.80
± 0.17
Moxifloxacin
Besifloxacin
Untreated
2
1
*
- Fewer CFU/cornea than besifloxacin treated or
untreated corneas (P ≤ 0.0001)
Conclusions
 Moxifloxacin was highly effective
prophylactically for MRSA within the
cornea or anterior chamber.
 Besifloxacin demonstrated insignificant
prophylactic effectiveness in the cornea
or the aqueous humor compared to
untreated eyes.