The Prophylactic The Prophylactic Effectiveness of Two Effectiveness of Two Fluoroquinolones on Fluoroquinolones on

Staphylococcus aureusStaphylococcus aureus in in Rabbit EyesRabbit Eyes

Balzli C, Caballero A, Tang A, Weeks A, Balzli C, Caballero A, Tang A, Weeks A, O’Callaghan RO’Callaghan R

University of Mississippi Medical Center, Microbiology Department, Jackson, MS

The authors of this poster have received research funding and travel The authors of this poster have received research funding and travel expenses from Alcon Laboratories Inc.expenses from Alcon Laboratories Inc.

IntroductionIntroduction Staphylococcus aureusStaphylococcus aureus represents a significant represents a significant

infectious agent causing keratitis and infectious agent causing keratitis and endophthalmitis associated with penetrating endophthalmitis associated with penetrating surgery (i.e. cataract surgery).surgery (i.e. cataract surgery).

S. aureusS. aureus, particularly methicillin-resistant , particularly methicillin-resistant S. S. aureusaureus (MRSA), infections can be very (MRSA), infections can be very damaging to the eye and is increasingly difficult damaging to the eye and is increasingly difficult to treat.to treat.

Topical fluoroquinolones are commonly used Topical fluoroquinolones are commonly used prophylactically and as treatment for such prophylactically and as treatment for such infections due to their spectrum of coverage infections due to their spectrum of coverage and overall activity, as well as their ability to and overall activity, as well as their ability to penetrate tissues.penetrate tissues.

IntroductionIntroduction The effectiveness of fluoroquinolones has been The effectiveness of fluoroquinolones has been

demonstrated many times in experimental MRSA demonstrated many times in experimental MRSA keratitis models.keratitis models.

In the past, gauging the bactericidal effectiveness of In the past, gauging the bactericidal effectiveness of these drugs on these drugs on S. aureusS. aureus in the anterior chamber has in the anterior chamber has relied on relied on in vitroin vitro data such as drug concentrations in data such as drug concentrations in the aqueous humor and minimum inhibitory the aqueous humor and minimum inhibitory concentrations (MIC) because concentrations (MIC) because S. aureusS. aureus typically dies typically dies within the rabbit anterior chamber.within the rabbit anterior chamber.

In these studies, a clinical isolate of MRSA was found In these studies, a clinical isolate of MRSA was found to grow in the anterior chamber and was used to to grow in the anterior chamber and was used to quantify the prophylactic bactericidal effectiveness of quantify the prophylactic bactericidal effectiveness of moxifloxacin and besifloxacin, a new fluoroquinolone, moxifloxacin and besifloxacin, a new fluoroquinolone, in the rabbit cornea and anterior chamber.in the rabbit cornea and anterior chamber.

Growth of MRSAGrowth of MRSA659659 in in the Anterior Chamberthe Anterior Chamber

Hours Post-InfectionHours Post-Infection

101066 CFU inoculum : n ≥ 3 / time point CFU inoculum : n ≥ 3 / time point

11223344556677

0.50.5 22 44 66 88 1010

LogC

FU/m

lLo

gCFU

/ml

USA300 – Community Acquired MRSA (Strain NRS659*)

* Network on Antimicrobial Resistance in * Network on Antimicrobial Resistance in S. aureusS. aureus

10hr PI10hr PI

MRSAMRSA659659 Susceptibility to Susceptibility to FluoroquinolonesFluoroquinolones

MICs of the commercial ophthalmic formulations of MICs of the commercial ophthalmic formulations of moxifloxacin (0.5%) and besifloxacin (0.6%) were moxifloxacin (0.5%) and besifloxacin (0.6%) were determined.determined.

0.03 0.03 µg/mlµg/mlbesifloxacinbesifloxacin

0.06 0.06 µg/mlµg/mlmoxifloxacinmoxifloxacinn = 6

After determining the growth and susceptibility After determining the growth and susceptibility of MRSA659, the prophylactic effectiveness of of MRSA659, the prophylactic effectiveness of the two fluoroquinolones were tested in keratitis the two fluoroquinolones were tested in keratitis and endophthalmitis infection models in the and endophthalmitis infection models in the rabbit eye.rabbit eye.

Prophylactic Prophylactic TreatmentTreatment

30 min 30 min

Infect cornea or Infect cornea or anterior chamberanterior chamber

Topical application Topical application of drug (45 of drug (45 µl)µl)

Rinse eye Rinse eye with PBSwith PBS

Quantify CFU of Quantify CFU of anterior chamberanterior chamber

Treatment GroupsTreatment Groups::0.6% 0.6% besifloxacin besifloxacin ((BesivanceBesivance) 45 ) 45 µlµl0.5% 0.5% moxifloxacin moxifloxacin ((VigamoxVigamox) 45 ) 45 µlµlUntreatedUntreated

3030 Minute Minute Prophylaxis of Prophylaxis of

MRSA KeratitisMRSA Keratitis

22

33

44

55

66

UntreatedUntreatedMoxifloxacinMoxifloxacin BesifloxacinBesifloxacin

Log

CFU

/Cor

nea

Log

CFU

/Cor

nea

**

** - Fewer CFU/cornea than besifloxacin treated or - Fewer CFU/cornea than besifloxacin treated or untreated corneas (P untreated corneas (P ≤ 0.0023)≤ 0.0023)

Inoculation = 10Inoculation = 1066 CFU : n = 4/group CFU : n = 4/group

5.98± 0.05

4.01± 0.22

5.72± 0.21

11

22

33

44

55

66

MoxifloxacinMoxifloxacin BesifloxacinBesifloxacin UntreatedUntreated

Log

CFU

/ml A

queo

usLo

g C

FU/m

l Aqu

eous

3030 Minute Prophylaxis Minute Prophylaxis of MRSA of MRSA

EndophthalmitisEndophthalmitis

**

** - Fewer CFU/cornea than besifloxacin treated or - Fewer CFU/cornea than besifloxacin treated or untreated corneas (P untreated corneas (P ≤ 0.0001)≤ 0.0001)

Inoculation = 10Inoculation = 1066 CFU : n = 8/group CFU : n = 8/group

4.80± 0.17

5.01± 0.14

3.30± 0.12

ConclusionsConclusions Moxifloxacin was highly effective Moxifloxacin was highly effective

prophylactically for MRSA within the prophylactically for MRSA within the cornea or anterior chamber.cornea or anterior chamber.

Besifloxacin demonstrated insignificant Besifloxacin demonstrated insignificant prophylactic effectiveness in the cornea prophylactic effectiveness in the cornea or the aqueous humor compared to or the aqueous humor compared to untreated eyes. untreated eyes.