The Dose & Administration of Intracameral Moxifloxacin (note: all intracameral antibiotic use is...
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Transcript of The Dose & Administration of Intracameral Moxifloxacin (note: all intracameral antibiotic use is...
SA Research
The Dose & Administration ofIntracameral Moxifloxacin
(note: all intracameral antibiotic use is off-label)
Steve A. Arshinoff MD FRCSCHumber River Regional Hospital
Departments of Ophthalmology and Vision Sciences,University of Toronto & McMaster University
Financial Disclosures :
Alcon Laboratories Inc. - Consultant
Poster P10 Submission # 981672
SA Research
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. Review of ophthalmologic and microbiologic literature and
current practices, as well as experience to date.
SA Research
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
G4 fluoroquinolones - Gatifloxacin 100 µg
- Moxifloxacin 100-500 µg
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.
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.
SA Research
Published intracameral cephalosporin studies all show 80-90+% endophthalmitis rate
reduction with use of intracameral cephalosporins.
Study IC Antibiotic years nPOENo IC
POEIC
rate p
1Garat, Barcelona
Cefazolin2.5 mg/0.1ml
2004 -2007
18,603 1/240 1/2,130 0.047% <0.001
2RomeroReus, Spain
Cefazolin1mg/0.1 ml
2001 -2004
7,268 1/160 1/1,809 0.055% <0.001
3Montan,Sweden
Cefuroxime1mg/0.1 ml
1990 -2000
66,200 1/383 1/1,600 0.06% <0.001
4Wejde,Sweden, NCR
Cefuroxime1mg/0.1ml.
1999-2001
188,151 1/454 1/1,887 0.053% <0.001
5Lundström,Sweden NCR
Cefuroxime1mg/0.1 ml
2002 –2004
225,471 1/290 1/2,231 0.045% <0.001
6Barry,ESCRS Study
Cefuroxime 1mg/0.1ml
2003 -2006
16,603 1/337 1/1,621 0.07% <0.001
7Garcia –SaenzMadrid, Spain
Cefuroxime1.0 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
NCR = Swedish national cataract registry, POE = Post –Operative Endophthalmitis, IC = intracameral antibiotic
SA Research
Are other intracameral antibioticsbetter 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
*p
Immediately Sequential Bilateral Cataract Surgeries only 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% <0.0001
*The incidence of postoperative endophthalmitis after immediately sequential bilateral cataract surgery. 2011 in press
*p = www.openepi.com 2 tailed Mid p exact
SA Research
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.
*** Montan PG, Wejde G, Setterquist H et al. Prophylactic intracameral cefuroxime. Evaluation of safety and kinetics in cataract surgery. JCRS 2002; 28: 982-987.
SA Research
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.
•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.
SA Research
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.
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
SA Research
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
Steve A. Arshinoff MD FRCSCHumber River Regional Hospital
University of Toronto & McMaster UniversityEmail: [email protected]
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.