Transcript The Dose & Administration of Intracameral Moxifloxacin

The Dose & Administration of
Intracameral Moxifloxacin
(note: all intracameral antibiotic use is off-label)
Steve A. Arshinoff MD FRCSC
SA
Research
Humber River Regional Hospital
Departments of Ophthalmology and Vision Sciences,
University of Toronto & McMaster University
Financial Disclosures :
Alcon Laboratories Inc. - Consultant
Poster P10
Submission
# 981672
The Dose & Administration of Intracameral Moxifloxacin
Purpose:
1.
To assess the desirability of moxifloxacin as an intracameral
antibiotic for endophthalmitis prophylaxis.
2.
To determine the optimal dose of intracameral moxifloxacin
based upon best available current evidence
Methods:
1.
SA
Research
Review of ophthalmologic and microbiologic literature and
current practices, as well as experience to date.
Intracameral antibiotic prophylaxis:
Drugs that have been used & reported.
Class
Drug
Dose / 0.1 cc
Complex Glycopeptide
- Vancomycin
1 mg
Cephalosporins:
- Cefazolin (G1)
1- 2.5 mg
- Cefuroxime (G2)
1 mg
- Gatifloxacin
100 µg
- Moxifloxacin
100-500 µg
G4 fluoroquinolones
SA
Research
Recent Intracameral Cephalosporin Data
As Baseline Reference for Infection Rates
• Due to promotion of the ESCRS study protocol and results6, the best
baseline data to estimate current infection rates with and without
intracameral antibiotics, comes from numerous recent studies of
intracameral cephalosporins.
• The table on the following slide illustrates a weight-averaged sum
(weighted by numbers of cases) and risks of endophthalmitis reported in
these studies1-7.
1Garat
M, Moser CL, Martin-Baranera M, Alonso-Tarres C, Alvarez-Rubio L. Prophylactic intracameral cefazolin after cataract surgery:
Endophthalmitis risk reduction and safety results in a 6-year study. JCRS 2009; 35: 637-42.
2Romero
P, Mendez I, Salvat M, et al. Intracameral cefazolin as prophylaxis against endophthalmitis in cataract surgery. J Cataract Refract Surg 2006:
32: 438-441 (March).
3Montan
PG, Wejde G, Koranyi G, Rylander M. Prophylactic Intracameral Cefuroxime. JCRS 2002; 28: 977-981, 982-7.
4Wejde
G, Montan P, Lundstrom M, Stenevi U, Thorburn W. Endophthalmitis following cataract surgery in Sweden: national prospective survey 1999-2001. Acta
Ophthalmol Scand 2005; 83:7-10.
5Lundstrom
M, Wejde G, Stenevi U et al. Endophthalmitis after cataract surgery: A nationwide prospective study evaluating incidence in relation to
incision type and location. Ophthalmology 2007; 114:886-870
6ESCRS
Endophth. Study group. Prophylaxis of postoperative endophthalmitis following cataract surgery: Results of the ESCRS multicenter study
and identification of risk factors. JCRS 2007; 33:978-988.
SA
Research
7García-Sáenz
MC, Arias-Puente A, Rodríguez-Caravaca G, Bañuelos JB. Effectiveness of intracameral cefuroxime in preventing endophthalmitis
after cataract surgery: Ten year comparative study. JCRS 2010; 36 203-7.
Published intracameral cephalosporin studies all show
80-90+% endophthalmitis rate reduction with use of
intracameral cephalosporins.
Study
IC Antibiotic
years
n
POE
No IC
POE
IC
rate
p
1Garat,
Cefazolin
2.5 mg/0.1ml
2004 2007
18,603
1/240
1/2,130
0.047%
<0.001
Cefazolin
1mg/0.1 ml
2001 2004
7,268
1/160
1/1,809
0.055%
<0.001
Cefuroxime
1mg/0.1 ml
1990 2000
66,200
1/383
1/1,600
0.06%
<0.001
Cefuroxime
1mg/0.1ml.
19992001
188,151
1/454
1/1,887
0.053%
<0.001
Cefuroxime
1mg/0.1 ml
2002 –
2004
225,471
1/290
1/2,231
0.045%
<0.001
ESCRS Study
Cefuroxime
1mg/0.1ml
2003 2006
16,603
1/337
1/1,621
0.07%
<0.001
–Saenz
Madrid, Spain
Cefuroxime
1.0 mg/0.1 ml
1999 2008
13,652
1/169
1/2,352
0.043%
<0.001
Sum
Weight averaged
90 - 08
535,948
1/331
1/1,977
0.05%
<0.001
Barcelona
2Romero
Reus, Spain
3Montan,
Sweden
4Wejde,
Sweden, NCR
5Lundström,
Sweden NCR
6Barry,
7Garcia
SA
Research
NCR = Swedish national cataract registry,
POE = Post –Operative Endophthalmitis,
IC = intracameral antibiotic
Are other intracameral antibiotics
better than cefuroxime?
• The ESCRS study did not compare efficacy of different IC
antibiotics. It tested only IC cefuroxime.
• We have collected data, over the past 2 years from bilateral
cataract surgeons, members of the iSBCS (international Society of
Bilateral Cataract Surgeons), on their unilateral and bilateral
procedures with all antibiotic regimens, a summary of which
appears on the next slide.
• Although huge numbers are needed to prove superiority of one
antibiotic over another, because of the extremely low incidence of
post-operative endophthalmitis in all groups, both vancomycin and
moxifloxacin tended to have lower infection rates than cefuroxime.
SA
Research
Endophthalmitis in Bilateral Cataract Surgery
2010 study*
IC Antibiotic
N (eyes)
Endophalmitis
(POE) cases
POE
rate
POE
rate
Immediately Sequential Bilateral Cataract Surgeries only
*p
vs. no IC
No IC antibiotic
23,847
12
1:1,987
0.05%
reference
Cefuroxime (cef)
45,873
5
1:9,175
0.01%
<0.01
Vancomycin
15,240
0
0
0
<0.01
Moxifloxacin
10,094
0
0
0
0.001
Immediately & Delayed Sequential Bilateral Cataract Surgeries
vs. cef.
Vancomycin
19,722
0
0
0
0.17
Moxifloxacin
35,194
1
1:35,194
0.003%
0.22
Moxifloxacin & Vancomycin
552
0
0
0
All IC antibiotic cases (vs. no IC)
101,341
6
1:16,890
0.006%
SA
Research
<0.0001
*p = www.openepi.com 2 tailed Mid p exact
*The incidence of postoperative endophthalmitis after immediately sequential bilateral cataract surgery. 2011 in press
Intracameral moxifloxacin
•
*Usual MIC of Staphylococci to moxifloxacin = 0.06 mg./L
•
We had used intracameral injections of 100 µg in 0.1 cc. in over 3,500 cases
without any infections.
•
In January 2010, one patient developed unilateral post-operative endophthalmitis
with a resistant strain of Staphylococcus epidermidis, MIC 8mg/L., 133x higher
than usual MIC!
•
**MIC90 for Staphylococci to moxifloxacin has been reported as high as 32 mg/L.
•
***Montan et al: Aqueous concentrations of antibiotics drop by 50% every ½ hour.
•
The following slide shows the calculation of IC moxifloxacin doses & effect.
*Balzli CL, Caballero AR, Tang A, Weeks AC, O’Callaghan RJ. Penetration and effectiveness of prophylactic
fluoroquinolones in experimental methicillin-sensitive or methicillin-resistant Staphylococcus aureus anterior chamber
infection. J Cataract Refract Surg 2010; 36:2160–2167.
** Miller D, Flynn PM, Scott IU, Alfonso EC, Flynn HW. In Vitro Fluoroquinolone Resistance in Staphylococcual
Endophthalmitis isolates. Arch Ophthalmol. 2006; 124: 479-483.
SA
Research
*** Montan PG, Wejde G, Setterquist H et al. Prophylactic intracameral cefuroxime. Evaluation of safety and kinetics in
cataract surgery. JCRS 2002; 28: 982-987.
Intracameral moxifloxacin
Moxifloxacin Dose
100 µg in 0.1cc.
300 µg in 0.2cc
500 µg in 0.1cc
Final AC concentration
330 mg / L
1000 mg / L
1660 mg / L
AC concentration – 1 hour
82 mg / L
250 mg / L
415 mg /L
AC concentration – 2 hours
20 mg / L
62 mg / L
104 mg /L
AC concentration – 3 hours
5 mg / L
16 mg / L
26 mg / L
AC concentration – 4 hours
1 mg / L
4 mg / L
6.5 mg / L
= < MIC of Our case;
= <MIC90 Miller et al endophthalmitis resistant isolates
•It is clear from the above that our previous moxifloxacin dose was likely inadequate to
eradicate resistant strains of Staphylococci, despite the rapid dose dependent bactericidal
effect of moxifloxacin.
•The 500 µg/0.1 cc. (direct from the bottle of eye drops) has the disadvantage of a less
physiologic solution for intracameral injection compared to the 300 µg/0.2 cc, which is a
mixture of 3 cc Vigamox® from the bottle diluted with 7 cc BSS.
SA
Research
•We have therefore chosen to use 300 µg/0.2 cc as our routine, as a compromise of
bactericidal efficacy and safety for the endothelium.
Does moxifloxacin have advantages over
cefuroxime and vancomycin?
1. Readily available as non-preserved eye drops (Vigamox®, Alcon).
2. Uncomplicated to dilute.

Desired dose = 150 µgm/0.1 cc. (use 0.2 cc. yielding 1 mg./ml in AC.

Aspirate 3 ml Vigamox® + 7 ml BSS in 12 cc. syringe. Millipore filter not needed.
3. Dose dependent (not time dependent bactericidal activity).
4. Broad antibacterial spectrum of activity of moxifloxacin.
SA
Research

Better than cefuroxime or vancomycin

*Even if an infection occurs, it will likely be moxifloxacin resistant Staphylococcus,
which is very sensitive to the usual endophthalmitis protocol of vancomycin and
ceftazidime, whereas infections that occur with intracameral cefuroxime are often
with destructive resistant bacteria , such as enterobacter.
5. Drug allergy very rare with moxifloxacin.
* Personal communication: Per Montan MD
Current anti-infective protocol – SAA
• Vigamox® gtts
- 1 gtt q 15 min x 4 preop
• Betadine gtts
- 5% solution 10 min preop.
• Betadine scrub
- 10% solution prep used to paint eye preop.
• moxifloxacin intracameral, intracapsular at end of case.
- 150µg in 0.2 cc BSS ( 1 mg/ml in AC)
• Vigamox® gtts
- 1 gtt 6x/d x 3 days,
- then QID x 7 days.
SA
Research
The Dose & Administration of Intracameral Moxifloxacin
Conclusions:
1. Moxifloxacin appears to offer the best
option of currently available antibiotics
for intracameral antibacterial
prophylaxis.
2. The optimal dose, based upon
experience to date, seems to be 150
µg/0.1 cc, diluted 3:7 with balanced salt
solution, with the administration of 0.2 cc
intracamerally, into the capsular bag, as
the final step in cataract surgery.
SA
Research
Steve A. Arshinoff MD FRCSC
Humber River Regional Hospital
University of Toronto & McMaster University
Email: [email protected]